chr4-61930576-A-G

Variant names:

• chr4-61930576-A-G
• rs2122646
• NM_001387552.1:c.2113-4264A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387552.1(ADGRL3):​c.2113-4264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,976 control chromosomes in the GnomAD database, including 31,056 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31056 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820
• Publications: 2 publications found

Genes affected

ADGRL3 (HGNC:20974): (adhesion G protein-coupled receptor L3) This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors (GPCR). Latrophilins may function in both cell adhesion and signal transduction. In experiments with non-human species, endogenous proteolytic cleavage within a cysteine-rich GPS (G-protein-coupled-receptor proteolysis site) domain resulted in two subunits (a large extracellular N-terminal cell adhesion subunit and a subunit with substantial similarity to the secretin/calcitonin family of GPCRs) being non-covalently bound at the cell membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.2113-4264A>G		intron_variant	Intron 13 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.2113-4264A>G		intron_variant	Intron 13 of 26		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95813 AN: 151858 Hom.: 31051 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.631 AC: 95845 AN: 151976 Hom.: 31056 Cov.: 32 AF XY: 0.622 AC XY: 46177 AN XY: 74270

African (AFR) AF: 0.526 AC: 21810 AN: 41438

American (AMR) AF: 0.566 AC: 8642 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2312 AN: 3466

East Asian (EAS) AF: 0.376 AC: 1942 AN: 5166

South Asian (SAS) AF: 0.535 AC: 2573 AN: 4808

European-Finnish (FIN) AF: 0.674 AC: 7108 AN: 10552

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49394 AN: 67960

Other (OTH) AF: 0.645 AC: 1364 AN: 2114

Alfa AF: 0.674 Hom.: 4181

Bravo AF: 0.618

Asia WGS AF: 0.453 AC: 1574 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.22
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2122646; hg19: chr4-62796294;